Since Schumpeter’s (The theory of economic development, 1934) seminal work on economic development, innovation is considered as one of the main drivers of firm performance and economic growth. At the same time, technological innovations vary considerably in terms of impact with only a minority of new inventions contributing significantly to technological progress and economic growth. More recently a number of indicators derived from patent documents have been advanced to capture the nature and impact of technological inventions. In this paper, we compare and validate these indicators within the field of biotechnology. An extensive analysis of the recent history of biotechnology allows us to identify the most important inventions (n = 214) that shaped the field of biotechnology in the time period 1976–2001. A considerable number of these inventions have been patented between 1976 and 2001 (n = 117, 55 %). For all USPTO biotech patents filed between 1976 and 2001 (n = 84,119), relevant indicators have been calculated. In a subsequent step, we assess which indicators allow us to distinguish between the most important patented inventions and their less influential counterparts by means of logistic regression models. Our findings show that the use of multiple, complementary indicators provides the most comprehensive picture. In addition, it is clear that ex-post indicators reflecting impact and value outperform ex-ante indicators reflecting the nature and novelty of the invention in terms of precision and recall.